Method and composition for use as an x-ray contrast material in the diagnosis of reflux peptic esophagitis



United States Patent METHOD AND COMPOSITION FOR USE AS AN X-RAY CONTRAST MATERIAL IN THE DIAG- N 0518 OF REFLUX PEPTIC ESOPHAGITIS Perry Hookman, Greenbelt, Md., assignor to Clinical Research Institute, Inc., Washington, D.C., a corporation of Washington, D.C.

No Drawing. Continuation-impart of application Ser. No. 537,312, Mar. 25, 1965. This application Aug. 19, 1968, Ser. No. 753,701

Int. Cl. A61k 27/08 U.S. Cl. 4244 7 Claims ABSTRACT OF THE DISCLOSURE A method is provided for diagnosing reflux peptic esophagitis by orally administering an X-ray contrast composition having a pH of from 1.5 to 2.7 and simultaneously taking an X-ray or fluoroscopic examination of the esophagus of the patient.

This application is a continuation-in-part of application Ser. No. 537,312, filed Mar. 25, 1966, now abandoned.

The present invention relates to an X-ray contrast media composition and, more particularly, to an X-ray contrast composition useful in the diagnosis of reflux peptic esophagitis.

Reflux peptic esophagitis is an abnormal condition resulting from an acid condition in the esophagus which gives symptoms of chest pains and marked heartburn. In reflux esophagitis the gastric stomach contents are refluxed from the stomach back into the esophagus causing erosion and ulceration of the esophagus and resulting in a great deal of pain and internal distress. Normal people do not ordinarily suffer from this reflux in a very significant amount. The diagnosis of this condition is important because the symptoms are similar to other abrnormal conditions, such as coronary insufficiency, which are totally unrelated to reflux esophagitis.

Until the present time the diagnosis of reflux peptic esophagitis has been relatively diflicult embodying the acidperfusion test, a technique not normally carried out in the oflice of a general practitioner or internist due to its relative complexity. The acid-perfusion test generally requires the placement of a tube through the nose of the patient and into the esophagus and the dripping of 0.1 N HCl down into the esophagus through the tube. The abnormal patient, suffering from reflux esophagitis, suflers both pain and/or spasms. The normal patient, not suflering from reflux esophagitis, does not suffer either spasms or the heartburn'like pain. However, the acid-perfusion test is not only diflicult for the physician, but it is even uncomfortable for the normal patient.

It is therefore an object of the present invention to obviate and/or alleviate the problems of the prior art, such as indicated above.

It is another object of the present invention to provide an X-ray contrast composition particularly suitable for the diagnosis of reflux peptic esophagitis.

It is another object of the present invention to provide an improved method of diagnosing reflux pipetic esophagitis.

It is another object of the present invention to provide a packaged composition which can be easily and consistently used without variation in properties by general practitioners, internists, radiologists and allied specialists for the accurate diagnosis of reflux peptic esophagitis.

It is another object of the present invention to provide for the more simplified and accurate diagnosis of reflux peptic esophagitis.

These and other objects and the nature and advantages of the present invention will be more apparent from the following detailed description.

In accordance with the present invention it has now been found that an X-ray or fluoroscope technique may be easily used to more accurately diagnose reflux peptic esophagitis by feeding to the patient a composition comprising an X-ray contrast medium, i.e., an aqueous suspension of an X-ray opaque material, mixed with suflicient acid to provide the composition with a pH in the range of from 1.5 to 2.7 and preferably 1.7-2.0. After feeding the patient the above composition, the esophagus may then be X-rayed according to conventional X-ray practice and without the necessity of utilizing past procedures for the diagnosis of reflux esophagitis.

The present technique provides great simplicity in its use and also more accurately diagnoses reflux esophagitis according to the following factors which are easily determined on the fluoroscope or on X-rays:

(1) There is an increase in simultaneous contractions of the esophagus;

(2) There is a rise in the base line of intraluminal pressure of the esophagus;

(3) There is marked reflux of the contrast medium in the esophagus with the result that the contrast medium, such as barium sulfate, will be shot both up and down the esophagus instead of just down; and

(4) There will be a delay in the interval time between the onset of swallowing and the final arrival of the peristaltic wave in the lower esophagus.

Preferably, the contrast medium utilized in the aqueous suspension of the present invention is barium sulfate. However, any conventional contrast medium may be used.

The acid used to acidify the aqueous suspension of contrast medium is preferably hydrochloric acid, since this is both the natural stomach acid and it is a sufliciently strong acid. However, any strong organic or inorganic acid which is nonpoisonous may be used if desired so long as it is capable of reducing the pH of the mixture to at least 2.7 and preferably to 2.0 or below. Among these other acids which may be used are acetic acid, citric acid and the like. It will be understood that certain of the weaker of the usable acids must be used in greater concen tration than the stronger acids. Approximately 10-20 cc. of the acetic or citric acid is added to cc. of the aqueous suspension of barium sulfate. Among those acids which cannot be used because they are either too Weak or poisonous, or both, are carbolic acid (phenol), arsenic acid, boric acid, oxalic acid, chromic acid and other-s. While a suitable acid may be chosen from known acids, it will be understood that hydrochloric acid is the preferred acid.

Besides the X-ray contrast medium, preferably an aqueous suspension of barium sulfate, and the acid, preferably BC], the composition may also include further additives, if desired which are non-essential. Thus, taste modifying materials may be added as Well as various types of fillers such as cellulosic material or gelatinous materials, and preservatives such as methylparaben.

In use, the composition is fed to the patent in a quantity of from 25-100 cc., preferably 25-50 cc. and the esophagus is simultaneously X-rayed or fluoroscoped. If the patient sufliers from reflux esophagitis, (l) the increased contractions, (2) the rise in the base line of intraluminal pressure, (3) the reflux of contrast medium, and (4) the delay from the normal 5 Seconds to the abnormal 20-25 seconds between the onset of swallowing the composition and the final arrival of the peristaltic wave in the lower esophagus will be shown on the fluoroscope or the X-rays.

For use by general practitioners, internists, radiologists, and allied specialists, it is desirable to package the acidified composition in collapsible containers preferably formed of acid-resistant plastic material. A sterile plastic tube, similar to a conventional toothpaste tube, formed of a nylon or a polyolefin, and containing 100 cc. of the acidified contrast material, is particularly suitable. In this manner, the physician need not mix his own composition and take the chance of having a nonsterile or improperly acidified batch.

The following examples, in which amounts of all materials are expressed in parts by volume unless otherwise indicated, will illustrate the manner in which the invention can be practiced. However, it is to be understood that the specific features set forth are not to be considered limiting of the invention. In the following examples, unless otherwise indicated the barium sulfate suspension consist of 33% parts by weight of USP (XVII) barium sulfate with water added to yield 100 cc.

Example I Twenty patients, known to have reflux peptic esophagitis, were split into two groups of ten patients each. As a control, the first group was tested with unaltered aqueous barium sulfate suspension. The second group was treated with a mixture of 2.5 volumes of 1 normal HCl and 100 volumes of the barium sulfate suspension. The quantities of the mixture fed to the patients was varied between 25 and 100 cc.

Upon observation through the fluoroscope or upon observing X-rays of the two groups, it was shown that the unacidified barium sulfate suspension would not increase simultaneous contractions of the esophagus, would not raise the base line of intraluminal pressure of the esophagus, would not reflux in the esophagus and would not delay the rate of the peristaltic Wave. The strongly acidified barium sulfate suspension, on the other hand, consistently provided an increase in simultaneous contractions, a rise in the base line of intraluminal pressure, marked reflux of the barium sulfate, and a delay of from 15 to 20 seconds (to 20-25 seconds) between the onset of swallowing and the final arrival of the peristaltic Wave in the lower esophagus.

Example II Numerous other tests were run to determine the suitability of using different acids and different pHs. Among the various different acids used are citric and acetic acids. Both prove satisfactory so long as the pH is maintaned at a value not to exceed 2.7, although results are more positive when the pH is maintained at a lower level. Various proportions of hydrochloric acid are also effective so long as the pH is maintained at a value not exceeding 2.7 and preferably below 2.

Suspension agents which may be added to the compositions include gum tragacanth, magnesium aluminum silicate clay, gum karaya, monooleate of sor-bitan polyethylene glycol, sodium montmorillonite, bentonite, agar, sodium alginate, methyl cellulose and the like. The amount of suspension agents can be varied between 13.5%.

Flavoring agents which can be used include dextrose, orange oil, syntharone, lactose, malted milk, saccharin, sucrose, powdered sugar and the like.

The percentage of USP barium sulfate in the aqueous suspension can vary between 2040% by weight. USP barium sulfate has an average particle size less than 4 microns. Large particle barium sulfate having a particle .4 size of between 4 and 12 microns may also be used, so long as the purity is maintained.

Other specific compositions which may be used are as follows:

Aqueous suspension of USP (XVII) barium sulfate containing 40% by weight barium sulfate cc Conc. hydrochloric acid (1 normal) cc 2 Aqueous suspension containing 35% by weight USP (XVII) barium sulfate cc 100 Monooleate of sorbitan polyethylene glycol g 9.8

In tests which were conducted using X-ray contrast agents with pH values greater than 2.7 for the diagnosis of peptic reflux esophagitis it was found that as the pH value increases over 2.7 that there are many false negatives in the patients who indeed do have esophagitis documented by other tests who will not show the manifestations enumerated heretofore. Accordingly, it is critical that the pH of the compositions according to the present invention not exceed 2.7. Further, it was found that when the pH is decreased below 1.5 that there are false positives found in the patients. Accordingly, it is also critical that the pH of the compositions not be less than 1.5.

What is claimed is:

1. A method of diagnosing reflux peptic esophagitis whereby contractions of the esophagus and reflux of the barium sulfate indicates the presence of the condition comprising orally administering 25-100 cc. of an acidified X-ray contrast medium to a patient, said medium comprising an aqueous suspension of barium sulfate containing 20-40% by weight barium sulfate in the suspension and sufficient hydrochloric acid to yield a pH of the resulting suspension of from 1.5-2.7, and simultaneously taking an X-ray or fluoroscopic examination of the esophagus of said patient, as the medium is orally administered.

2. The method of claim 1, wherein the pH of the medium administered is below 2.0.

3. The method of claim 1, wherein the pH of the medium administered is about 1.72.0.

4. A composition for use in diagnosing reflux peptic esophagitis comprising an aqueous suspension of barium sulfate containing 20-40% by weight of barium sulfate in the suspension and suflicient acid selected from the group consisting of hydrochloric acid, acetic acid and citric acid to yield a pH of the resulting suspension of from 1.5-2.7.

5. A composition according to claim 4, wherein the pH is below 2.0.

6. A composition according to claim 4, wherein the pH is about 1.7-2.0.

7. A composition according to claim 4, wherein the acidifying acid is hydrochloric acid.

References Cited UNITED STATES PATENTS 2,659,690 11/1953 Slaybaugh 424-4 ALBERT T. MEYERS, Primary Examiner.

F. E. WADDELL, Assistant Examiner. 

